Schistosoma mansoni:Genetic Restriction and Cytokine Profile of the CD4 + T Helper Cell Response to Dominant Epitope Peptide of Major Egg Antigen Sm-p40

Abstract

Hernandez, H. J., Edson, C. M., Harn, D. A., Ianelli, C. J., and Stadecker, M. J. 1998.Schistosoma mansoni: Genetic restriction and cytokine profile of the CD4+ T helper cell response to dominant epitope peptide of major egg antigen Sm-p40.Experimental Parasitology90, 122–130. Granuloma formation in schistosomiasis is mediated by MHC class II-restricted CD4 + T helper lymphocytes sensitized to egg antigens. We previously reported that C3H mice, which develop large granulomas, display strong CD4 + T helper cell responses to the major egg antigen Sm-p40. Moreover, all members of a panel of egg antigen-specific T cell hybridomas responded to the Sm-p40 antigen. Given the significance of the Sm-p40 molecule in the C3H T cell repertoire against schistosomal egg antigens, the current work was undertaken to map its immunogenic epitopes, using a library of 15 synthetic overlapping 30-mer peptides. The dominant epitope recognized by polyclonal CD4 + Th cells was located in peptide 10 (amino acids 229–258); subdominant epitopes were detected in peptides 8 (amino acids 179–208) and 12 (amino acids 279–308). The anti-Sm-p40 T cell hybridomas variously responded to any one of the same three stimulatory peptides. Furthermore, studies with various mouse strains demonstrated that a strong anti-Sm-p40 response was restricted by H-2k. Interestingly, the cells responding to peptide 10 and to the Sm-p40 antigen only secreted IL-2 and IFN-γ, but not IL-4 and IL-10, indicating that they are entirely of the Th-1-type, a subset with demonstrated capacity to mediate egg granuloma formation. The identification of dominant epitopes within key egg antigens offers opportunities for desensitization of the CD4 + Th cells that mediate pathology in schistosomia sis.